Single-cell analysis reveals innate lymphoid cell lineage infidelity in atopic dermatitis - 03/02/22
, Wolfgang M. Bauer, MD a, ∗, Thomas Krausgruber, PhD b, Issac Goh, BSc c, Johannes Griss, MD, PhD a, Vy Nguyen, MSc a, Baerbel Reininger a, Christine Bangert, MD a, Clement Staud, MD d, Patrick M. Brunner, MD, MSc a, Christoph Bock, PhD b, e, Muzlifah Haniffa, MD, PhD c, f, g, Georg Stingl, MD aAbstract |
Background |
Although ample knowledge exists about phenotype and function of cutaneous T lymphocytes, much less is known about the lymphocytic components of the skin’s innate immune system.
Objective |
To better understand the biologic role of cutaneous innate lymphoid cells (ILCs), we investigated their phenotypic and molecular features under physiologic (normal human skin [NHS]) and pathologic (lesional skin of patients with atopic dermatitis [AD]) conditions.
Methods |
Skin punch biopsies and reduction sheets as well as blood specimens were obtained from either patients with AD or healthy individuals. Cell and/or tissue samples were analyzed by flow cytometry, immunohistochemistry, and single-cell RNA sequencing or subjected to in vitro/ex vivo culture.
Results |
Notwithstanding substantial quantitative differences between NHS and AD skin, we found that the vast majority of cutaneous ILCs belong to the CRTH2+ subset and reside in the upper skin layers. Single-cell RNA sequencing of cutaneous ILC-enriched cell samples confirmed the predominance of biologically heterogeneous group 2 ILCs and, for the first time, demonstrated considerable ILC lineage infidelity (coexpression of genes typical of either type 2 [GATA3 and IL13] or type 3/17 [RORC, IL22, and IL26] immunity within individual cells) in lesional AD skin, and to a much lesser extent, in NHS. Similar events were demonstrated in ILCs from skin explant cultures and in vitro expanded ILCs from the peripheral blood.
Conclusion |
These findings support the concept that instead of being a stable entity with well-defined components, the skin immune system consists of a network of highly flexible cellular players that are capable of adjusting their function to the needs and challenges of the environment.
Le texte complet de cet article est disponible en PDF.Graphical abstract |
Key words : Innate lymphoid cells, atopic dermatitis, human skin, single-cell RNA sequencing
Abbreviations used : AD, AHR, GATA3, HC, ILC, ILC1, ILC2, ILC3, NHS, PB, PE, RORA, RORC, scRNA-seq, TSLP
Plan
| Supported by grants from the Austrian Science Fund (FWF; DK W 1248-B30) and the Medical University of Vienna, as well as by grant IF_2017_29 from the innovation fund of the Austrian Academy of Sciences (to G.S.) and, in part, by grant 18130 from the Medical Scientific Fund of the Mayor of the City of Vienna (to G.S.). |
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| Disclosure of potential conflict of interest: The authors declare that they have no relevant conflicts of interest. |
Vol 149 - N° 2
P. 624-639 - février 2022 Retour au numéro
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